Levin E R, Mills S, Weber M A
Peptides. 1986 Nov-Dec;7(6):977-81. doi: 10.1016/0196-9781(86)90124-5.
Endogenous opioids have been implicated as modulators of the central nervous system regulation of blood pressure and heart rate. Whether these neuropeptides participate in blood pressure regulation in hypertension is unknown. To begin to study this question, we examined the response to opiate antagonists and agonists in the spontaneously hypertensive rat (SHR) and the normotensive Wistar-Kyoto (WKY) rat. The long-acting opiate antagonist naltrexone, 2.5 micrograms/kg, was injected into the lateral ventricle of the brain in awake, freely-moving SHR and produced a significant 19 mmHg decrease in mean arterial blood pressure compared to basal blood pressure (p less than 0.01); a decrease was not observed at a two logarithm lower dose. In contrast, naltrexone had no effect on the blood pressure of normotensive Wistar-Kyoto (WKY) rats. To evaluate a possible regulatory role for the predominantly kappa receptor active opioids, alpha- and beta-neo-endorphin, 10 micrograms each, was administered to SHR on separate days by intracerebroventricular injection. alpha- and beta-neo-endorphin caused significant decreases in mean arterial blood pressure of 11 and 9 mmHg respectively, effects reversed by pre-treatment with the opiate antagonist, naloxone. Heart rate was unaffected by any of the injected opioids or antagonists. Our naltrexone results support the hypothesis that an endogenous opioid(s) contributes to the hypertensive state of the SHR. Additionally, alpha- and beta-neo-endorphin can lower blood pressure in this model.
内源性阿片肽被认为是中枢神经系统调节血压和心率的调节剂。这些神经肽是否参与高血压患者的血压调节尚不清楚。为了开始研究这个问题，我们检测了自发性高血压大鼠（SHR）和正常血压的Wistar-Kyoto（WKY）大鼠对阿片拮抗剂和激动剂的反应。将2.5微克/千克的长效阿片拮抗剂纳曲酮注射到清醒、自由活动的SHR的脑侧脑室中，与基础血压相比，平均动脉血压显著降低了19 mmHg（p<0.01）；在低两个对数剂量时未观察到血压下降。相比之下，纳曲酮对正常血压的Wistar-Kyoto（WKY）大鼠的血压没有影响。为了评估主要作用于κ受体的活性阿片肽α-和β-新内啡肽可能的调节作用，在不同的日子通过脑室内注射给SHR分别给予10微克的α-和β-新内啡肽。α-和β-新内啡肽分别使平均动脉血压显著降低11 mmHg和9 mmHg，这些作用可被阿片拮抗剂纳洛酮预处理逆转。心率不受任何注射的阿片类药物或拮抗剂的影响。我们关于纳曲酮的研究结果支持这样的假设，即内源性阿片肽促成了SHR的高血压状态。此外，在这个模型中，α-和β-新内啡肽可以降低血压。
